Figure 9. Fructose utilization mediated by GLUT5 influences the activity of AMPK/mTORC1 signaling in LC.

(A) Phospho-protein profiling showing enhanced phosphorylation of AMPK and ACC1 and decreased phosphorylation of 4E-BP1, P70S6K, and S6 in A549 tumor xenograft with SLC2A5 deletion as relative to control A549 tumor xenograft. (B) Western blot approach validating the phosphorylation states of AMPK, ACC1, and 4E-BP1 between A549 tumor xenografts with SLC2A5 deletion and control A549 tumor xenografts. (C) RNA-Seq analysis showing repressed transcription of downstream target genes of mTORC1 signaling in A549 tumor xenografts with SLC2A5 abrogation. (D and E) Impact of fructose and glucose on AMPK (D) and 4E-BP1 (E) phosphorylation of A549 cells with or without SLC2A5 ablation. Control A549 cells and A549 cells with SLC2A5 deletion were starved in sugar-free medium for 2 hours and then were treated with 6 mM fructose or 6 mM glucose for 1 hour. Subsequently, cells were harvested for analysis. (F) The influence of an AMPK agonist, AICAR, on phosphorylation status of AMPK and 4E-BP1 in A549 cells cultured in fructose medium. Cells were treated with 1 mM AICAR or vehicle for 6 hours. Samples from the same batch were run at different times. The corresponding loading controls were shown for each measurement. (G) The influence of AICAR (1 mM) on proliferation of A549 cells cultured in fructose medium. Cumulative data were shown; n = 3. Data shown as mean ± SEM. **P < 0.01, 2-tailed Student’s t test.